Putting human stem cells in animal embryos? The NIH should get on board.

By Henry T. Greely

Apr 07, 2016 | 5:00 AM

Mythological chimeras such as the half-man, half-lion sphinx are fearsome creatures, but in real life, scientists have made human/nonhuman chimeras for decades to help millions of people. Above, the Great Sphinx in Egypt. (Associated Press)

Thirty years ago Paul Simon immortalized one of the first animal-human transplants with the lyrics, "These are the days of miracle and wonder.… Medicine is magical and magical is art. Thinking of the boy in the bubble and the baby with the baboon heart." Today we face the possibility of babies getting organs grown in human/nonhuman chimeras — beasts that are pigs except for a single human organ. To the uninitiated, this may sound more like the dark arts than modern medicine, but pursuing careful research and potential clinical use of these chimeras is both proper and important.

Every day about 30 Americans die because they can't get an organ transplant. Upward of 120,000 Americans are on transplant waiting lists. We are, medically, on the cusp of being able to save these lives in new ways: repairing failing organs with new genes or stem cells, building mechanical organs and growing replacement organs.

The latter holds the most promise for scaling up to meet the need. Growing organs inside humans for harvest is, thankfully, only the stuff of dystopian science fiction. Doing it in labs is being tried but is difficult. But there is another plausible alternative: growing human organs in other animals.

At the Salk Institute in San Diego, leading stem cell researcher Juan Carlos Izpisua Belmonte wants to grow a human pancreas in a pig to provide insulin-making cells for transplant into diabetics. His research into how this can be accomplished is exciting but very early, yet even those preliminary steps have been threatened by a surprise moratorium announced last fall by the National Institutes of Health. NIH said it would not fund any research that involved putting human stem cells into earliest-stage nonhuman embryos. NIH said this wasn't a ban, but just a pause to consider the implications of such research and possibly to create a policy for it.

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In early November, NIH held a workshop to discuss the issue; I moderated one of the panels and can report that the speakers uniformly favored this research, although with some limits. And yet so far no policies, and no funding, have come out of NIH.

Can we successfully grow human organs in pigs for transplant? Maybe, or maybe not.

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Can we successfully grow human organs in pigs for transplant? Maybe, or maybe not. The idea is if you put some human stem cells into a pig embryo genetically engineered not to grow the desired organ, the human cells might build one to fill the void. Belmonte has had what he calls "spectacular" results using this approach to grow rat organs in mice. That's no guarantee that human organs will grow in pigs, but we won't find out if Belmonte and others can't try.

Doctors and scientists have made human/nonhuman chimeras for decades. Millions of people across the world are alive because of replacement heart valves, many taken from pigs' hearts, others carved from cartilage from cattle. And scientists regularly put human tissue into nonhuman animals, especially rats and mice, for lab research.

So why is NIH getting cold feet? Even after the November workshop, that's not clear. The agency appears to be worried about public backlash, but about what?

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Is the public widely concerned about the welfare of pigs raised to be sacrificed for humans? That's a tough position for a carnivorous society to take. The bigger source of unease surely has ancient roots, reaching back to chimeras from myth and religion: the sphinx, the Minotaur, and many gods mix species. Hundreds of stories, novels and films have taught us that crossing those boundaries ends badly. But in our real, nonfiction world, should we care?

It likely depends on how "human" the chimera seems. A pig with a human heart, liver, or kidney will still seem to be a pig. Our feelings might change if a pig had a human brain, or produced human eggs or sperm, or somehow looked human.

Most stem cell research done in the United States already has safeguards. Experiments are regulated by embryonic stem cell research oversight committees (or, in California, by very similar stem cell research oversight committees).

Among the rules and guidelines these committees apply are those issued in 2005 by the National Academy of Sciences. These demand that in approving research projects committees consider where stem cells are likely to go in an animal, and what kinds of cells they are likely to become. They are specifically on the lookout for "too human" chimeras.

NIH has not specifically required the researchers it funds to adhere to the 2005 National Academy guidelines on chimeras. But it can. And that should quell its reservations about using human stem cells in animals. We have an effective system for regulating this kind of research. NIH shouldn't be holding back experiments that, among other valuable results, might eventually solve the transplant organ shortage.

The NIH funding moratorium was imposed more than six months ago. It is time for it to be lifted, in the hope that people awaiting organ transplants in the future will experience more of Paul Simon's "days of miracle and wonder."

Henry T. Greely is a law professor at Stanford and director of its Center for Law and the Biosciences, and the Stanford Program in Neuroscience and Society. He also chairs California's Human Stem Cell Research Advisory Committee.